rs140462332

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_001843.4(CNTN1):​c.2598C>G​(p.Ala866Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,613,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

CNTN1
NM_001843.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.303

Publications

0 publications found
Variant links:
Genes affected
CNTN1 (HGNC:2171): (contactin 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
CNTN1 Gene-Disease associations (from GenCC):
  • Compton-North congenital myopathy
    Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
  • schizophrenia
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 12-41025224-C-G is Benign according to our data. Variant chr12-41025224-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 258195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.303 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00112 (171/152242) while in subpopulation AFR AF = 0.00366 (152/41540). AF 95% confidence interval is 0.00318. There are 0 homozygotes in GnomAd4. There are 76 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNTN1NM_001843.4 linkc.2598C>G p.Ala866Ala synonymous_variant Exon 21 of 24 ENST00000551295.7 NP_001834.2 Q12860-1A0A024R104

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNTN1ENST00000551295.7 linkc.2598C>G p.Ala866Ala synonymous_variant Exon 21 of 24 1 NM_001843.4 ENSP00000447006.1 Q12860-1
CNTN1ENST00000347616.5 linkc.2598C>G p.Ala866Ala synonymous_variant Exon 20 of 23 1 ENSP00000325660.3 Q12860-1
CNTN1ENST00000348761.2 linkc.2565C>G p.Ala855Ala synonymous_variant Exon 19 of 22 1 ENSP00000261160.3 Q12860-2
CNTN1ENST00000550305.1 linkn.557C>G non_coding_transcript_exon_variant Exon 5 of 6 3

Frequencies

GnomAD3 genomes
AF:
0.00112
AC:
171
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000721
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000957
GnomAD2 exomes
AF:
0.000366
AC:
92
AN:
251082
AF XY:
0.000280
show subpopulations
Gnomad AFR exome
AF:
0.00400
Gnomad AMR exome
AF:
0.000521
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000120
AC:
175
AN:
1461704
Hom.:
1
Cov.:
31
AF XY:
0.000105
AC XY:
76
AN XY:
727156
show subpopulations
African (AFR)
AF:
0.00299
AC:
100
AN:
33456
American (AMR)
AF:
0.000447
AC:
20
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5764
European-Non Finnish (NFE)
AF:
0.0000333
AC:
37
AN:
1111882
Other (OTH)
AF:
0.000282
AC:
17
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
12
25
37
50
62
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00112
AC:
171
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.00102
AC XY:
76
AN XY:
74436
show subpopulations
African (AFR)
AF:
0.00366
AC:
152
AN:
41540
American (AMR)
AF:
0.000720
AC:
11
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000882
AC:
6
AN:
68022
Other (OTH)
AF:
0.000947
AC:
2
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
9
19
28
38
47
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000535
Hom.:
1
Bravo
AF:
0.00128
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Mar 10, 2020
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

CNTN1: BP4, BP7 -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Compton-North congenital myopathy Benign:1
Nov 18, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
8.7
DANN
Benign
0.75
PhyloP100
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs140462332; hg19: chr12-41419026; API